Abstract: Objective To explore the potential mechanism of Xuebijing Injection in the treatment of sepsis, based on network pharmacology and molecular docking. Methods The Swiss Target Prediction and TCMSP databases were used to predict the drug ingredients and targets of Xuebijing Injection, and screen the core components. The STITCH, DisGeNET and Genecards databases were used to predict the targets of sepsis. The Venny 2.1.0 tool was used to create a Venn diagram for the intersection of common targets of Xuebijing Injection treatment and sepsis, and a protein-protein interaction (PPI) network was established to screen out the core targets. The DAVID database was utilized to obtain the related pathways by KEGG and GO enrichment analyses, and the signaling pathways with high relevance based on the P value of the entries were screencd out. Then, the core components and core targets were used for molecular docking by Chem 3D, AutoDock, and Pymol software, in order to further explain the mechanism of Xuebijing Injection in the treatment of sepsis at the molecular level. Results A total of 113 potential targets of Xuebijing Injection for sepsis were screened and obtained. According to PPI network analysis,the top five core targets based on the degree value were interleukin (IL)-1β, IL-6, protein kinase B (AKT)1, tumor protein P53 (TP53), and vascular endothelial growth factor A (VEGFA). GO and KEGG enrichment analyses showed that Xuebijing Injection involved multiple signaling pathways in sepsis treatment, which mainly included IL-17, tumor necrosis factor (TNF), hypoxia inducible factor (HIF)-1 signaling pathways and Th17 cell differentiation, among which the IL-17 signaling pathway was highly enriched. Finally, through molecular docking, we found that the docking binding energies of quercetin, kaempferol, and mignonin (the top three core components of Xuebijing Injection) with IL-1β, IL-6, and TP53 were all less than -5 kcal/mol, which indicated that quercetin, kaempferol, and mignonin were able to bind better with the core targets, with better binding ability. Conclusions Xuebijing Injection is characterized by "multi-component, multi-target, and multi-pathway". Quercetin, kaempferol and lignans may be the main active ingredients of Xuebijing Injection. IL-1β, IL-6 and TP53 proteins may be the potential therapeutic targets of Xuebijing Injection in the treatment of sepsis. Xuebijing Injection may play a therapeutic role through the IL-17, TNF and HIF-1 signaling pathways and Th17 cell differentiation.